AGE AND CONTROL OF HUMAN SKIN BLOOD FLOW

描述（改编自申请人摘要）：皮肤 循环在人体体温调节中起着不可或缺的作用。 有 真皮基质中与年龄相关的内在变化， 血管，以及自主控制血流，其中的任何一个或全部可以 改变皮肤血管对局部和全身热的反应 压力 根据Grant AG 07004 -01至-05进行的研究 表明在热应激期间，皮肤血流量的增加 （SkBF）和身体核心中每摄氏度增量的皮肤血管传导性 在健康活跃的男女中， 与20-30岁的受试者相比，55岁。 这种减量 似乎是由于外围而不是中心（例如，下丘脑） 年龄相关的变化。 然而，许多关于衰老的问题仍然存在， 控制皮肤血液流动。 人体SkBF对升高的体重的反应 温度是独特的，因为有一个发达的活性 交感血管扩张系统以及肾上腺素能血管收缩剂 系统 在任何给定的环境影响下， 这两个竞争系统之间的关系决定了净SkBF，但它是 不知道哪个系统被老化过程改变了。 当地 溴苄铵甲苯磺酸盐离子电渗疗法-消除血管收缩剂 影响，从而允许活性血管扩张剂的研究 在没有收缩器效应的情况下，提供了一种工具， 这是为了检查内在的影响的机制， 在SkBF控制下老化。 此外，干预措施旨在 增加老年受试者的热诱导血管舒张， 被检查过了 因此，拟议的续设 格兰特AG- 07004是系统地研究年龄的影响， 控制人体皮肤的血液流动，以及年龄的机制- 相关变化。 具体研究假设如下：1）体内 最大SkBF随年龄增长而降低; 2）传出通路 与衰老引起的血管舒张反应减弱有关的是 主动血管扩张系统; 3）年龄相关的SkBF下降可能是 通过运动训练减弱; 3a）负责的机制是 在给定的核心温度下增强的血管舒张系统活性; 4）在 绝经后妇女，雌激素（E2）替代治疗增加SkBF 在给定的核心温度下; a）该响应继发于E2- 诱发等渗性高血容量症。

DESCRIPTION (Adapted from the applicant's abstract): The cutaneous circulation plays an integral role in human thermoregulation. There are intrinsic age-related changes in the dermal matrix, in the cutaneous vessels, and in autonomic control of blood flow, any or all of which may alter the cutaneous vascular response to local and whole-body thermal stresses. Studies performed under Grant AG07004-01 through -05 demonstrated that during heat stress, the increase in skin blood flow (SkBF) and skin vascular conductance per degree C increment in body core temperature is markedly attenuated in healthy active men and women over the age of 55, when compared to 20-30 year- old subjects. This decrement appears to be due to peripheral rather than central (e.g., hypothalamic) age-related changes. However, many questions remain about aging and control of skin blood flow. The human SkBF response to elevated body temperature is unique in that there is a well developed active sympathetic vasodilator system as well as an adrenergic vasoconstrictor system. Under any given set of environmental influences, the balance between these two competing systems determines the net SkBF, yet it is not known which system is altered by the aging process. The local iontophoresis of bretylium tosylate - which eliminates vasoconstrictor influences, and thus allows for the study of the active vasodilator system in the absence of constrictor effects - provides a tool with which to examine the mechanisms underlying the effects of intrinsic aging on control of SkBF. In addition, interventions aimed at increasing thermally-induced vasodilation in older subjects have not been examined. Therefore, the scope of the proposed continuation of Grant AG- 07004 is to systematically study the effects of age on the control of human skin blood flow, and the mechanisms underlying the age- related changes. Specific research hypotheses are as follows: 1) In vivo maximal SkBF decreases with advancing age; 2) The efferent pathway involved in the attenuated vasodilatory response with aging is the active vasodilator system; 3) The age- related decline in SkBF can be attenuated by exercise training; 3a) The mechanism responsible is enhanced vasodilator system activity at a given core temperature; 4) In post-menopausal women, estrogen (E2) replacement therapy increases SkBF at a given core temperature; a) This response is secondary to an E2- induced isotonic hypervolemia.